Lenize Costa Reis Marins de Carvalho

Antihypertensive, vasodilator and antioxidant effects of a vinifera grape skin extract.

Cumulative evidence suggests that moderate wine consumption exerts a cardioprotective effect. We investigated the occurrence of an antihypertensive effect of an alcohol‐free hydroalcoholic grape skin extract (GSE) obtained from skins of a vinifera grape (Vitis labrusca) in experimental rodent hypertension models. The vasodilator effect of GSE (polyphenols concentration 55.5 mg g−1) was also assessed in the isolated mesenteric vascular bed of Wistar rats and the antioxidant effect was studied on lipid peroxidation of hepatic microsomes. Oral administration of GSE significantly reduced systolic, mean and diastolic arterial pressure in Wistar rats with desoxycorticosterone acetate‐salt and NG‐ nitro‐L‐arginine methyl ester (L‐NAME) induced experimental hypertension. In the rat isolated mesenteric vascular bed pre‐contracted with norepinephrine, bolus injections of GSE induced endothelium‐dependent vasodilatation that was substantially inhibited by L‐NAME, but not by indometacin, tetraethylammonium or glibenclamide. Lipid peroxidation of hepatic microsomes estimated as malondialdehyde production was concentration‐dependently inhibited by GSE. In conclusion, the antihypertensive effect of GSE might be owing to a combination of vasodilator and antioxidant actions of GSE. These findings also suggest that the beneficial effect of moderate red wine consumption could be owing to an antihypertensive action induced by compounds occurring in the skin of vinifera grapes.

Bronchodilator activity of Mikania glomerata Sprengel on human bronchi and guinea‐pig trachea

The effects of aqueous extracts and hydro‐alcoholic extract (HAE), and of a dichloromethane fraction (MG1) obtained from the HAE of Mikania glomerata leaves on isolated respiratory and vascularsmooth muscle have been investigated. Aqueousextracts and HAE induced a significant inhibition on the histamine contractions on the isolated guinea‐pig trachea. HAE extract induced a concentration‐dependent relaxation on guinea‐pig trachea pre‐contracted with histamine (IC50 0.34 (0.29‐0.39) mg mL−1), acetylcholine (IC50 0.72 (0.67‐0.77) mg ml−1) or K+ (IC50 1.41 (1.18‐1.64) mg mL−1) and on isolated human bronchi precontracted with K+ (IC50 0.34 (0.26‐0.42) mg mL−1). The dichloromethane fraction induced a concentration dependent relaxation in guinea‐pig trachea precontracted with K+ (IC50 0.017 (0.012‐0.022) mg mL−1). The dichloromethane fraction had also a small vasodilator effect on the isolated mesenteric vascular bed and on the isolated rat aorta, and a significant reduction of the oedema induced by subplantar injections of Bothrops jararaca venom in mice. When tested on plasmid DNA, MG1 did not damage the DNA. Chromatographic analysis showed the presence of 11.4% w/w coumarin in MG1. The results supported the indication of M. glomerata products for the treatment of respiratory diseases where bronchoconstriction is present.

Antioxidant treatment with tempol and apocynin prevents endothelial dysfunction and development of renovascular hypertension.

BACKGROUND Two-kidney-one-clip (2K-1C) rats develop renovascular hypertension associated with endothelial dysfunction and elevated levels of oxidative stress. The role of oxidative damage is unknown in vascular dysfunction coupled with 2K-1C hypertension. The aims of this study were to evaluate the effects of chronic treatment with a superoxide dismutase (SOD) mimetic (tempol) and an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase (apocynin) on the development of hypertension, endothelial dysfunction, and oxidative damage in 2K-1C rats. METHODS 2K-1C rats and sham-operated rats were treated with tempol or apocynin for 40 days, while the corresponding nontreated groups received tap water. Blood pressure (BP), mesenteric arterial reactivity, plasma and mesentery oxidative damage, mesenteric protein expression, and antioxidant activities were compared among the four groups. RESULTS Chronic treatment with tempol (1 mmol/l) or apocynin (33 microg/kg/day) impaired the development of hypertension in 2K-1C rats and did not change the BP in control animals. The reduction in vasodilatory effect induced by acetylcholine (ACh) in the mesenteric arterial beds (MABs) of 2K-1C rats was restored by tempol and apocynin. Plasma and mesentery levels of malondialdehyde (MDA) were higher in 2K-1C rats, and these levels were significantly reduced by the administration of tempol and apocynin. Mesenteric SOD activity and expression were higher in 2K-1C rats than in the controls, and treatment with tempol resulted in a reduction in SOD activity. CONCLUSIONS The data suggest that a compromised mechanism of antioxidant defense and an increase in oxidative damage contribute to the development of hypertension and associated vascular dysfunction in 2K-1C rats, and that tempol and apocynin prevent these effects.

Protective effect of Euterpe oleracea Mart (açaí) extract on programmed changes in the adult rat offspring caused by maternal protein restriction during pregnancy

This study examined the effect of açaí (Euterpe oleracea Mart.) seed extract (ASE) on cardiovascular and renal alterations in adult offspring, whose mothers were fed a low‐protein (LP) diet during pregnancy.

Euterpe oleracea Mart.-Derived Polyphenols Protect Mice from Diet-Induced Obesity and Fatty Liver by Regulating Hepatic Lipogenesis and Cholesterol Excretion

The aim of this study was to investigate the effect of a polyphenol-rich Açaí seed extract (ASE, 300 mg/kg-1d-1) on adiposity and hepatic steatosis in mice that were fed a high-fat (HF) diet and its underlying mechanisms based on hepatic lipid metabolism and oxidative stress. Four groups were studied: C57BL/6 mice that were fed with standard diet (10% fat, Control), 10% fat + ASE (ASE), 60% fat (HF), and 60% fat + ASE (HF + ASE) for 12 weeks. We evaluated the food intake, body weight gain, serum glucose and lipid profile, hepatic cholesterol and triacyglycerol (TG), hepatic expression of pAMPK, lipogenic proteins (SREBP-1c, pACC, ACC, HMG-CoA reductase) and cholesterol excretion transporters, ABCG5 and ABCG8. We also evaluated the steatosis in liver sections and oxidative stress. ASE reduced body weight gain, food intake, glucose levels, accumulation of cholesterol and TG in the liver, which was associated with a reduction of hepatic steatosis. The increased expressions of SREBP-1c and HMG-CoA reductase and reduced expressions of pAMPK and pACC/ACC in HF group were antagonized by ASE. The ABCG5 and ABCG8 transporters expressions were increased by the extract. The antioxidant effect of ASE was demonstrated in liver of HF mice by restoration of SOD, CAT and GPx activities and reduction of the increased levels of malondialdehyde and protein carbonylation. In conclusion, ASE substantially reduced the obesity and hepatic steatosis induced by HF diet by reducing lipogenesis, increasing cholesterol excretion and improving oxidative stress in the liver, providing a nutritional resource for prevention of obesity-related adiposity and hepatic steatosis.

Role of renin–angiotensin system and oxidative status on the maternal cardiovascular regulation in spontaneously hypertensive rats

BACKGROUND The purpose of this study was to investigate the contribution of renin-angiotensin system (RAS) and oxidative status on the maternal cardiovascular regulation at the end of pregnancy in normotensive and spontaneously hypertensive rats (SHR). METHODS Blood pressure (BP), mesenteric arterial bed (MAB) reactivity, mesenteric oxidative damage, protein expression, and antioxidant activities were compared between four groups: SHR (SHR-P) and normotensive Wistar controls (W-P) in the 20th day of pregnancy or age-matched nonpregnant rats (SHR-NP and W-NP). RESULTS BP in W-P and SHR-P was reduced at the end of pregnancy. The vasodilator effects of angiotensin II (Ang II) and angiotensin 1-7 (Ang-(1-7)) were higher in SHR-P than in other groups. Endothelial nitric oxide synthase (eNOS) expression was increased in W-P and SHR-P compared to nonpregnant groups. Angiotensin-converting enzyme (ACE) and AT(1) receptor expressions were increased in SHR-NP compared to normotensive groups and pregnancy reduced their expressions in SHR. No difference was observed in AT(2) receptor expression among the groups. ACE2 expression was higher in hypertensive than normotensive groups. The levels of thiobarbituric acid-reactive substances (TBARS) were reduced in pregnant compared to nonpregnant groups. Superoxide dismutase (SOD) activity was reduced in SHR-P compared to SHR-NP. However, pregnancy increased catalase (CAT) and glutathione peroxidase (GPx) activities in normotensive rats and SHR, respectively. CONCLUSIONS The results suggest that the reduction of BP to normal values at the end of pregnancy in SHR may be related to an increased NO production and vasorelaxation to Ang II and Ang-(1-7) associated with decreased expression of vascular ACE and AT(1) receptors and oxidative status.

Differential responses of mesenteric arterial bed to vasoactive substances in L-NAME-induced preeclampsia: Role of oxidative stress and endothelial dysfunction

ABSTRACT To investigate the systemic and placental oxidant status as well as vascular function in experimental preeclampsia (PE) induced by nitro-L-arginine methyl ester (L-NAME). Fetal parameters and maternal blood pressure, proteinuria, mesenteric arterial bed (MAB) reactivity, and systemic and placental oxidative stress were compared between four groups: pregnant rats receiving L-NAME (60 mg/kg/day, orally) (P + L-NAME) or vehicle (P) from days 13 to 20 of pregnancy and nonpregnant rats receiving L-NAME (NP + L-NAME) or vehicle (NP) during 7 days. L-NAME administration during pregnancy induced some hallmarks of PE, such as hypertension and proteinuria. The P + L-NAME group presented lower weight gain and placental mass as well as reduced number and weight of live fetuses than P group. The vasodilator effect induced by acetylcholine (ACh) and angiotensin II (Ang II) was lower in the perfused MAB from NP + L-NAME and P + L-NAME than in control groups. Otherwise, the nitroglycerine-induced vasodilation and the phenylephrine- and Ang II-induced vasoconstriction were higher in MAB from NP + L-NAME and P + L-NAME groups than in the respective controls. Systemic and placental oxidative damage, assessed by malondialdehyde and carbonyl levels, was increased and activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were reduced in P + L-NAME and NP + L-NAME groups compared to controls. The present data suggest that the oxidative stress and reduced bioavailability of nitric oxide may contribute to attenuation of vasodilator responses to ACh and Ang II, and hyperreactivity to Ang II in the mesentery of preeclamptic rat, which may contribute to the increased peripheral vascular resistance and BP, as well as intrauterine growth restriction in L-NAME-induced PE.

The Beneficial Effect of Anthocyanidin‐Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High‐Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions

We hypothesized that a polyphenol‐rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high‐fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti‐inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF‐α, IL‐6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF‐fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright

Supplementation with Vitis vinifera L. skin extract improves insulin resistance and prevents hepatic lipid accumulation and steatosis in high-fat diet–fed mice

Nonalcoholic fatty liver disease is one of the most common complications of obesity. The Vitis vinifera L. grape skin extract (ACH09) is an important source of polyphenols, which are related to its antioxidant and antihyperglycemic activities. We hypothesized that ACH09 could also exert beneficial effects on metabolic disorders associated with obesity and evaluated ACH09s influence on high-fat (HF) diet-induced hepatic steatosis and insulin resistance in C57BL/6 mice. The animals were fed a standard diet (10% fat, control) or an HF diet (60% fat, HF) with or without ACH09 (200mg/[kg d]) for 12weeks. Our results showed that ACH09 reduced HF diet-induced body weight gain, prevented hepatic lipid accumulation and steatosis, and improved hyperglycemia and insulin resistance. The underlying mechanisms of these beneficial effects of ACH09 may involve the activation of hepatic insulin-signaling pathway because the expression of phosphorylated insulin receptor substrate-1, phosphatidylinositol 3-kinase, phosphorylated Akt serine/threonine kinase 1, and glucose transporter 2 was increased by ACH09 and correlated with improvement of hyperglycemia, hyperinsulinemia, and insulin resistance. ACH09 reduced the expression of the lipogenic factor sterol regulatory-element binding protein-1c in the liver and upregulated the lipolytic pathway (phosphorylated liver kinase B1/phosphorylated adenosine-monophosphate-activated protein kinase), which was associated with normal hepatic levels of triglyceride and cholesterol and prevention of steatosis. ACH09 prevented the hepatic oxidative damage in HF diet-fed mice probably by restoration of antioxidant activity. In conclusion, ACH09 protected mice from HF diet-induced obesity, insulin resistance, and hepatic steatosis. The regulation of hepatic insulin signaling pathway, lipogenesis, and oxidative stress may contribute to ACH09s protective effect.

Antidiabetic effect of Euterpe oleracea Mart. (açaí) extract and exercise training on high-fat diet and streptozotocin-induced diabetic rats: A positive interaction

A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression.